tbuckley/cabot-search huggingface dataset:
Fatal neonatal listeriosis following L. monocytogenes horizontal transmission highlights neonatal susceptibility to orally acquired listeriosis
Authors: Caroline Charlier, Coralie Noel, Lukas Hafner, Alexandra Moura, Claire Mathiaud, Aurélia Pitsch, Chakib Meziane, Lydie Jolly-Sanchez, Astrid de Pontfarcy, Sylvain Diamantis, Hélène Bracq-Dieye, Olivier Disson, Pierre Thouvenot, Guillaume Valès, Nathalie Tessaud-Rita, Mathieu Tourdjman, Alexandre Leclercq, Marc Lecuit
Journal: Cell Reports Medicine (2023)

We report a case of fulminant fatal neonatal listeriosis due to horizontal transmission of Listeria monocytogenes (Lm) in a neonatal double room. Genomic analyses reveal a close genetic relationship between clinical isolates, supporting cross-contamination. Oral inoculation experiments in adult and neonatal mice show that neonates are susceptible to a low Lm inoculum and that this susceptibility results from the immaturity of the neonatal gut microbiota. Infected neonates should therefore be isolated for as long as they shed Lm in their feces to avoid horizontal transmission and its dire consequences.
Tipping points in neurodegeneration
Authors: Mikael Simons, Johannes Levin, Martin Dichgans
Journal: Neuron (2023)

In Alzheimer's disease (AD), Aβ deposits form slowly, several decades before further pathological events trigger neurodegeneration and dementia. However, a substantial proportion of affected individuals remains non-demented despite AD pathology, raising questions about the underlying factors that determine the transition to clinical disease. Here, we emphasize the critical function of resilience and resistance factors, which we extend beyond the concept of cognitive reserve to include the glial, immune, and vascular system. We review the evidence and use the metaphor of "tipping points" to illustrate how gradually forming AD neuropathology in the preclinical stage can transition to dementia once adaptive functions of the glial, immune, and vascular system are lost and self-reinforcing pathological cascades are unleashed. Thus, we propose an expanded framework for pathomechanistic research that focuses on tipping points and non-neuronal resilience mechanisms, which may represent previously untapped therapeutic targets in preclinical AD.
Artificial intelligence in ophthalmology: The path to the real-world clinic
Authors: Zhongwen Li, Lei Wang, Xuefang Wu, Jiewei Jiang, Wei Qiang, He Xie, Hongjian Zhou, Shanjun Wu, Yi Shao, Wei Chen
Journal: Cell Reports Medicine (2023)

Artificial intelligence (AI) has great potential to transform healthcare by enhancing the workflow and productivity of clinicians, enabling existing staff to serve more patients, improving patient outcomes, and reducing health disparities. In the field of ophthalmology, AI systems have shown performance comparable with or even better than experienced ophthalmologists in tasks such as diabetic retinopathy detection and grading. However, despite these quite good results, very few AI systems have been deployed in real-world clinical settings, challenging the true value of these systems. This review provides an overview of the current main AI applications in ophthalmology, describes the challenges that need to be overcome prior to clinical implementation of the AI systems, and discusses the strategies that may pave the way to the clinical translation of these systems.
A suture-free, shape self-adaptive and bioactive PEG-Lysozyme implant for Corneal stroma defect repair and rapid vision restoration
Authors: Hang Zhou, Shaohua Zhang, Miao Lei, Yixin Cai, Honglei Wang, Jianguo Sun, Jingyuan Cui, Changsheng Liu, Xue Qu
Journal: Bioactive Materials (2023)

Corneal transplantation is a prevailing treatment to repair injured cornea and restore vision but faces the limitation of donor tissue shortage clinically. In addition, suturing-needed transplantation potentially causes postoperative complications. Herein, we design a PEG-Lysozyme injective hydrogel as a suture-free, shape self-adaptive, bioactive implant for corneal stroma defect repair. This implant experiences a sol-gel phase transition via an in situ amidation reaction between 4-arm-PEG-NHS and lysozyme. The physicochemical properties of PEG-Lysozyme can be tuned by the components ratio, which confers the implant mimetic corneal modulus and provides tissue adhesion to endure increased intraocular pressure. In vitro tests prove that the implant is beneficial to Human corneal epithelial cells growth and migration due to the bioactivity of lysozyme. Rabbit lamellar keratoplasty experiment demonstrates that the hydrogel can be filled into defect to form a shape-adaptive implant adhered to native stroma. The implant promotes epithelialization and stroma integrity, recovering the topology of injured cornea to normal. A newly established animal forging behavior test prove a rapid visual restoration of rabbits when use implant in a suture free manner. In general, this work provides a promising preclinical practice by applicating a self-curing, shape self-adaptive and bioactive PEG-Lysozyme implant for suture-free stroma repair.
Decreasing incidence of conjunctival squamous cell carcinoma in people with HIV in South Africa
Authors: Carole Metekoua, Yann Ruffieux, Victor Olago, Tafadzwa Dhokotera, Matthias Egger, Julia Bohlius, Eliane Rohner, Mazvita Muchengeti
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background The main risk factors for squamous cell carcinoma of the conjunctiva (SCCC) are immunodeficiency and exposure to ultraviolet radiation. Little is known about SCCC epidemiology among people with HIV (PWH) in South Africa. Methods We used data from the South African HIV Cancer Match study, a nation-wide cohort of PWH in South Africa, created through a privacy-preserving probabilistic record linkage of HIV-related laboratory records from the National Health Laboratory Service and cancer records from the National Cancer Registry from 2004 to 2014. We calculated crude incidence rates, analyzed trends using joinpoint models, and estimated hazard ratios for different risk factors using Royston-Parmar flexible parametric survival models. Results Among 5 247 968 PWH, 1059 cases of incident SCCC were diagnosed, for a crude overall SCCC incidence rate of 6.8 per 100 000 person-years. The SCCC incidence rate decreased between 2004 and 2014, with an annual percentage change of ‒10.9% (95% confidence interval: ‒13.3 to ‒8.3). PWH residing within latitudes 30°S to 34°S had a 49% lower SCCC risk than those residing at less than 25°S latitude (adjusted hazard ratio = 0.67; 95% confidence interval: 0.55 to 0.82). Other risk factors for SCCC were lower CD4 counts and middle age. There was no evidence for an association of sex or settlement type with SCCC risk. Conclusions An increased risk of developing SCCC was associated with lower CD4 counts and residence closer to the equator, indicative of higher ultraviolet radiation exposure. Clinicians and PWH should be educated on known SCCC preventive measures, such as maintaining high CD4 counts and protection from ultraviolet radiation through sunglasses and sunhats when outdoors.
Drug rediscovery in gastroenterology: from off-label to on-label use of thioguanine in inflammatory bowel disease
Authors: Nanne K H de Boer, Melek Simsek, Berrie Meijer, Markus F Neurath, Ad van Bodegraven, Chris J J Mulder
Journal: Gut (2023)

Drug rediscovery refers to the principle of using ‘old’ drugs outside the indications mentioned in the summary of product characteristics. In the past decades, several drugs were rediscovered in a wide variety of medical fields. One of the most recent examples is the unconditional registration of thioguanine (TG), a thiopurine derivative, in patients with inflammatory bowel disease in the Netherlands. In this paper, we aim to visualise potential hurdles that hamper drug rediscovery in general, emphasise the global need for optimal use and development of potentially useful drugs, and provide an overview of the registration process for TG in the Netherlands. With this summary, we aim to guide drug rediscovery trajectories in the near future.
Clinical outcome of pediatric medulloblastoma patients with Li–Fraumeni syndrome
Authors: Anna S Kolodziejczak, Lea Guerrini-Rousseau, Julien Masliah Planchon, Jonas Ecker, Florian Selt, Martin Mynarek, Denise Obrecht, Martin Sill, Robert J Autry, Eric Stutheit-Zhao, Steffen Hirsch, Elsa Amouyal, Christelle Dufour, Olivier Ayrault, Jacob Torrejon, Sebastian M Waszak, Vijay Ramaswamy, Virve Pentikainen, Haci Ahmet Demir, Steven C Clifford, Ed C Schwalbe, Luca Massimi, Matija Snuderl, Kristyn Galbraith, Matthias A Karajannis, Katherine Hill, Bryan K Li, Mike Walsh, Christine L White, Shelagh Redmond, Loizou Loizos, Marcus Jakob, Uwe R Kordes, Irene Schmid, Julia Hauer, Claudia Blattmann, Maria Filippidou, Gianluca Piccolo, Wolfram Scheurlen, Ahmed Farrag, Kerstin Grund, Christian Sutter, Torsten Pietsch, Stephan Frank, Denis M Schewe, David Malkin, Myriam Ben-Arush, Astrid Sehested, Tai-Tong Wong, Kuo-Sheng Wu, Yen-Lin Liu, Fernando Carceller, Sabine Mueller, Schuyler Stoller, Michael D Taylor, Uri Tabori, Eric Bouffet, Marcel Kool, Felix Sahm, Andreas von Deimling, Andrey Korshunov, Katja von Hoff, Christian P Kratz, Dominik Sturm, David T W Jones, Stefan Rutkowski, Cornelis M van Tilburg, Olaf Witt, Gaëlle Bougeard, Kristian W Pajtler, Stefan M Pfister, Franck Bourdeaut, Till Milde
Journal: Neuro-Oncology (2023)

Abstract Background The prognosis for Li–Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients. Methods In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated. Results The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup “SHH_3” (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively). Conclusions LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.
What are the advancements in surgery?
Authors: Jie Huang
Journal: International Journal of Surgery (2023)

Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan, 243 Dianmian Avenue,Wuhua District, Kunming city, Yunnan,China,650101. fax:+86-087165351281. E-mail address: [email protected] (J. Huang). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Why has Palantir been given an interim contract to work on an NHS patient data project?
Authors: David Wrigley
Journal: BMJ (2023)

The UK government's recent decision to award Palantir, a US based multinational company, a contract to work on a large NHS patient data project risks harming the NHS' reputation and may, unintentionally, cause patients to opt out of data sharing and thereby lead to harm.It's important to remember that patient data are invaluable.The data are used to decide where to locate new healthcare services, set standards for quality of care across the country, and for important research, which helps to develop new treatments.
Water matters: we must end the pollution of our rivers with sewage
Authors: Julian Sheather
Journal: BMJ (2023)

I was born on a houseboat on the upper reaches of the river Thames.Summer was spent in the river.Home from school I would tear off my uniform-torture wearing it in those hot, sunstruck classrooms-and hurl myself into the cool water.This was the Seventies.Although the river ran green or brown according to the day, it was clean.Despite the disbelief of onlookers, it was, biologically at least, safe to swim in.My father marvelled at the comparison with the London Thames he knew in the Forties and Fifties: a dead river, little more than a toxic, anaerobic sluice, foul with human and industrial waste.But as a kid I swam in water that trout were rumoured to haunt.It was so obviously progress, such a hands down win for the world-for the environment, for the liberty of summer, for the joy of being alive-that I took its continuance for granted.
Re: Matthew S. Ernst, Vishal Navani, J. Connor Wells, et al. Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-line Combination Therapies for Metastatic Renal Cell Carcinoma. Eur Urol. 2023;84:109–116
Authors: Meredith M. Regan, Michael B. Atkins, David F. McDermott
Journal: European Urology (2023)
Recent Advances in Systemic Therapy for Advanced Intrahepatic Cholangiocarcinoma
Authors: Changhoon Yoo, Jaewon Hyung, Stephen L Chan
Journal: Liver Cancer (2023)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The incidence of intrahepatic cholangiocarcinoma (IHCCA) is rising around the world. The disease is becoming a major global health issue. Conventionally, most patients with cholangiocarcinoma present with advanced disease and systemic therapy is the mainstay of treatment. This review discusses recent advances in systemic treatments for patients with IHCCA. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; The addition of durvalumab to a gemcitabine plus cisplatin regimen has significantly improved overall survival in the phase 3 TOPAZ-1 trial and is currently recommended as a standard first-line treatment. The phase 3 ABC-06 and phase 2b NIFTY trials have shown the benefit of second-line fluoropyrimidine plus oxaliplatin, and fluoropyrimidine plus nanoliposomal irinotecan, respectively. They have provided a treatment option for patients without actionable alterations who progressed to first-line therapy. For patients with actionable genomic alterations, including &lt;i&gt;FGFR2&lt;/i&gt; rearrangement, &lt;i&gt;IDH1&lt;/i&gt; mutation, &lt;i&gt;BRAF&lt;/i&gt; mutation, and &lt;i&gt;ERBB2&lt;/i&gt; amplification, targeted agents have shown encouraging efficacy in several phase 2–3 trials, and are recommended as subsequent treatments. Immune checkpoint inhibitors are being investigated for the treatment of previously treated patients, although only a small proportion of patients showed durable responses. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; Recent advances in systemic treatments have improved clinical outcomes in patients with advanced IHCCA. However, most patients eventually show resistance to the treatment, and tumor progression occurs within a year. Indeed, there should be further efforts to improve the outcomes of patients with advanced IHCCA.
RAD21 is the core subunit of the cohesin complex involved in directing genome organization
Authors: Yuao Sun, Xin Xu, Wenxue Zhao, Yu Zhang, Keyang Chen, Yongzheng Li, Xiaotian Wang, Mengling Zhang, Boxin Xue, Wanting Yu, Yingping Hou, Chaobin Wang, Wei Xie, Cheng Li, Daochun Kong, Shu Wang, Yujie Sun
Journal: Genome biology (2023)

Abstract Background The ring-shaped cohesin complex is an important factor for the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we use super-resolution imaging to reveal the unique role of cohesin subunit RAD21 in cohesin loading and chromatin structure regulation. Results We directly visualize that up-regulation of RAD21 leads to excessive chromatin loop extrusion into a vermicelli-like morphology with RAD21 clustered into foci and excessively loaded cohesin bow-tying a TAD to form a beads-on-a-string-type pattern. In contrast, up-regulation of the other four cohesin subunits results in even distributions. Mechanistically, we identify that the essential role of RAD21 is attributed to the RAD21-loader interaction, which facilitates the cohesin loading process rather than increasing the abundance of cohesin complex upon up-regulation of RAD21. Furthermore, Hi-C and genomic analysis reveal how RAD21 up-regulation affects genome-wide higher-order chromatin structure. Accumulated contacts are shown at TAD corners while inter-TAD interactions increase after vermicelli formation. Importantly, we find that in breast cancer cells, the expression of RAD21 is aberrantly high with poor patient survival and RAD21 forms beads in the nucleus. Up-regulated RAD21 in HeLa cells leads to compartment switching and up-regulation of cancer-related genes. Conclusions Our results provide key insights into the molecular mechanism by which RAD21 facilitates the cohesin loading process and provide an explanation to how cohesin and loader work cooperatively to promote chromatin extrusion, which has important implications in construction of three-dimensional genome organization.
The plasticity of fibroblasts: A forgotten player in the aging process
Authors: Antero Salminen
Journal: Ageing Research Reviews (2023)

Tissue-resident fibroblasts are mesenchymal cells which possess an impressive plasticity in their ability to modify their properties according to the requirements of the microenvironment. There are diverse subgroups of fibroblast phenotypes associated with different tissue pathological conditions, e.g., cancers, wound healing, and many fibrotic and inflammatory conditions. The heterogeneous phenotypes can be subdivided into fibrogenic and non-fibrogenic, inflammatory and immunosuppressive subtypes as well as cellular senescent subsets. A major hallmark of activated fibroblasts is that they contain different amounts of stress fibers combined with α-smooth muscle actin (α-SMA) protein, i.e., commonly this phenotype has been called the myofibroblast. Interestingly, several stresses associated with the aging process are potent inducers of myofibroblast differentiation, e.g., oxidative and endoplasmic reticulum stresses, extracellular matrix (ECM) disorders, inflammatory mediators, and telomere shortening. Accordingly, anti-aging treatments with metformin and rapamycin inhibited the differentiation of myofibroblasts in tissues. There is evidence that the senescent phenotype induced in cultured fibroblasts does not represent the phenotype of fibroblasts in aged tissues. Considering the versatile plasticity of fibroblasts as well as their frequency and structural importance in tissues, it does seem that fibroblasts are overlooked players in the aging process.
Antigenicity and adjuvanticity co-reinforced personalized cell vaccines based on self-adjuvanted hydrogel for post-surgical cancer vaccination
Authors: Tao He, Yiling Shi, Xiaorong Kou, Meiling Shen, Xiuqi Liang, Xinchao Li, Rui Wu, Yanjie You, Qinjie Wu, Changyang Gong
Journal: Biomaterials (2023)
Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: a nationwide registry study from the Italian Medicines Agency
Authors: Gian Matteo Rigolin, Pier Paolo Olimpieri, Valentina Summa, Simone Celant, Lydia Scarfò, Lucia Tognolo, Maria Pia Ballardini, Antonio Urso, Mariarosaria Sessa, Silvia Gambara, Francesca Cura, Monica Fortini, Paolo Ghia, Antonio Cuneo, Pierluigi Russo
Journal: Blood Cancer Journal (2023)

Abstract In this analysis we describe the effectiveness of first-line ibrutinib in 747 patients with chronic lymphocytic leukemia (CLL) and TP53 aberrations in a nationwide study with a 100% capture of patients who received the study drug. Median age was 71 years (range 32–95). An estimated treatment persistence rate of 63.4% (95% CI 60.0%-67.0%) and survival rate of 82.6% (95% CI 79.9–85.4%) were recorded at 24 months. Disease progression or death were the reasons for discontinuation in 182/397 patients (45.8%). A higher risk of treatment discontinuation was found to be associated with age, ECOG-PS and pre-existing heart disease, whereas ECOG ≥ 1, age ≥ 70 years and male sex were associated with an increased risk of death. Median post-progression overall survival (OS) was 12.2 months (95% CI 9.2–22.0). Post-discontinuation median OS in patients who discontinued ibrutinib for other reasons was not reached (95% CI 42.3 months – NA). Ibrutinib was an effective first-line treatment for CLL and TP53 aberrations in patients treated at large academic centers and community practice hospitals. Clinical characteristics at baseline may influence the effectiveness of ibrutinib, whereas the experience of prescribing centers and multi-hit or single-hit TP53 aberrations had no impact on outcome in this high-risk population.
Cost comparison of post-remission strategies in younger and older AML patients in France
Authors: Michael Mounie, Pierre-Yves Dumas, Sandra Liva-Yonnet, Didier Fabre, Thibault Leguay, Jean Galtier, Emilie Berard, Ramaroson Hanta, Véronique Gilleron, Sarah Bertoli, Arnaud Pigneux, Christian Récher, Nadège Costa
Journal: Blood Cancer Journal (2023)
Age and memory B cells at baseline are associated with risk of relapse and memory B-cell reappearance following anti-CD20 treatment in pediatric frequently-relapsing/steroid-dependent nephrotic syndrome
Authors: Manuela Colucci, Andrea Angeletti, Federica Zotta, Rita Carsetti, Francesca Lugani, Lucilla Ravà, Pietro Ravani, Francesco Emma, Gian Marco Ghiggeri, Marina Vivarelli
Journal: Kidney International (2023)
Neurotransmitter systems in the etiology of major neurological disorders: Emerging insights and therapeutic implications
Authors: Mallikarjuna Nimgampalle, Harshini Chakravarthy, Sapana Sharma, Shruti Shree, Anoop Ramachandra Bhat, Jangampalli Adi Pradeepkiran, Vasudharani Devanathan
Journal: Ageing Research Reviews (2023)
The N-degron pathway mediates lipophagy: The chemical modulation of lipophagy in obesity and NAFLD
Authors: Eui Jung Jung, Ki Woon Sung, Tae Hyun Bae, Hee-Yeon Kim, Ha Rim Choi, Sung Hyun Kim, Chan Hoon Jung, Su Ran Mun, Yeon Sung Son, Shin Kim, Young Ho Suh, Anna Kashina, Joo-Won Park, Yong Tae Kwon
Journal: Metabolism (2023)